Arctigenin alleviates ER stress via activatingAMPK

• Published in: 中国药理学报：英文版 2012, Vol.33 (7), p.941-952
• Main Author: Yuan GU Xiao-xiao SUN Ji-ming YE Li HE Shou-sheng YAN Hao-hao ZHANG Li-hong HU Jun-ying YUAN Qiang YU
• Format: Article
• Language: English
• Subjects: AMPK; ATP生物发光; Western印迹法; 内质网应激; 压力调节器; 布雷菲德菌素A; 细胞活力; 苷元
• ISSN: 1671-4083; 1745-7254

Aim： To investigate the protective effects of arctigenin （ATG）, a phenylpropanoid dibenzylbutyrolactone lignan from Arctium lappa L （Compositae）, against ER stress in vitro and the underlying mechanisms. Methods： A cell-based screening assay for ER stress regulators was established. Cell viability was measured using MTI- assay. PCR and Western blotting were used to analyze gene and protein expression. Silencing of the CaMKK[3, LKB1, and AMPK（xl genes was achieved by RNA interference （RNAi）. An ATP bioluminescent assay kit was employed to measure the intracellular ATP levels. Results： ATG （2.5, 5, and 10 μmol/L） inhibited cell death and unfolded protein response （UPR） in a concentration-dependent manner in cells treated with the ER stress inducer brefeldin A （100 nmol/L）. ATG （1, 5, and 10 μmol/L） significantly attenuated protein synthesis in cells through inhibiting mTOR-p7OS6K signaling and eEF2 activity, which were partially reversed by silencing AMPKα1 with RNAi. ATG （1-50 μmol/L） reduced intracellular ATP level and activated AMPK through inhibiting complex I-mediated respiration. Pretreatment of cells with the AMPK inhibitor compound C （25 μmol/L） rescued the inhibitory effects of ATG on ER stress. Furthermore, ATG （2.5 and 5 μmol/L） efficiently activated AMPK and reduced the ER stress and cell death induced by palmitate （2 mmol/L） in INS-115 cells. Conclusion： ATG is an effective ER stress alleviator, which protects cells against ER stress through activating AMPK, thus attenuating protein translation and reducing ER load.